These studies are targeted to define the biochemical mechanisms whereby age-dependent changes in regulation of intermediary metabolism perturb physiological control systems and, thus, lead to a failure to maintain homeostasis in the aged. Topics include: 1) effect of age on the regulation of the carbohydrate and fat oxidation; 2) mechanism of control of pyruvate dehydrogenase activity by phosphorylation/ dephosphorylation reactions; 3) loci of the defect in fatty acid oxidation in heart mitochondria from aged animals; and 4) mechanism of regulation of the tricarboxylate cycle, the major energy-yielding pathway. BIBLIOGRAPHIC REFERENCES: Hansford, R.G.: Studies on the effects of coenzyme A-SH:acetyl-coenzyme A, nicotinamide adenine dinucleotide and adenosine diphosphate: adenosine triphosphate ratios on the interconversion of active and inactive pyruvate dehydrogenase in isolated rat heart mitochondria. J. Biol. Chem. 251: 5483-5489, 1976. Hansford, R.G.: Studies on the inactivation of pyruvate dehydrogenase by palmitoylcarnitine oxidation in isolated rat heart mitochondria. J. Biol. Chem. 252: 1552-1560, 1977.